ABSTRACT
The major cell type of the epidermis is the keratinocyte. Mammalian epidermis is characterized histologically by four distinct layers, each representing a distinct stage in the differentiation of the keratinocyte. Keratins are the major gene product of the keratinocyte and belong to a family of structural proteins called intermediate filaments. The bullous skin diseases of epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EHK) have many common features including intra-epidermal blistering due to cytolysis of keratinocytes. The generation of transgenic mice with phenotypes resembling the human disorders led to the inference that these keratins were involved in the human skin diseases of EBS and EHK. Interestingly, while the expression of mutant keratins with large deletions produces an obvious phenotype in transgenic mice, the expression of keratin genes with point mutations has so far failed to generate a phenotype. In EHK mice the keratinocytes adjacent to hair follicles are much less prone to cytolysis.
